Nitric Acid → Nitrodenafil

HRID 1532138Notes

Reaction equation

HRID 1532138 reaction equation
[N+:1]([O-:4])(O)=[O:2].[CH2:5]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[NH:15][C:16](=[O:27])[C:17]2[N:22]([CH3:23])[N:21]=[C:20]([CH2:24][CH2:25][CH3:26])[C:18]=2[N:19]=1)[CH3:6].O>S(=O)(=O)(O)O>[CH2:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:1]([O-:4])=[O:2])=[CH:10][C:9]=1[C:14]1[NH:15][C:16](=[O:27])[C:17]2[N:22]([CH3:23])[N:21]=[C:20]([CH2:24][CH2:25][CH3:26])[C:18]=2[N:19]=1)[CH3:6]

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 962WaterHCID 1354014775-(2-Ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]-7-pyrimidinone

Product 1

HCID 135566056NitrodenafilYield 61%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

Concentrated nitric acid (0.5 ml) was added dropwise to a stirred solution of 5-(2-ethoxyphenyl)-1-methyl-3-n-propyl-1.6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (2.0 g, 0.0064 mol) in concentrated sulphuric acid (10 ml) at 0° C., and the resulting orange solution was stirred at room temperature for 18 hours. The reaction solution was then added dropwise to stirred ice and water (200 g) and the solid precipitate collected by filtration. This solid was then dissolved in dichloromethane (50 ml) and the solution washed successively with brine (2×30 ml) and water (30 ml), dried (Na2SO4) and evaporated under vacuum to give a yellow solid. Crystallisation from acetonitrile gave the title compound as yellow needles (1.40 g, 61%), m.p. 214-216° C. Found: C,57.35; H,5.21; N,19.49. C17H19N5O4 requires C,57.13; H,5.36; N,19.60%.

Workup

  1. additionThe reaction solution was then added dropwise
  2. filtrationthe solid precipitate collected by filtration
  3. dissolutionThis solid was then dissolved in dichloromethane (50 ml)
  4. washthe solution washed successively with brine (2×30 ml) and water (30 ml)
  5. dry with materialdried (Na2SO4)
  6. customevaporated under vacuum
  7. customto give a yellow solid
  8. customCrystallisation from acetonitrile

Sources & evidence

ORD record
ord-b25c91bc255643c49d332e0b12588b0f
Source dataset
uspto-grants-2001_03
Patent number
US06200980B1

Reaction notes

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